Does implementation matter if comprehension is lacking? A qualitative investigation into perceptions of advance care planning in people with cancer

Purpose: While advance care planning holds promise, uptake is variable and it is unclear how well people engage with or comprehend advance care planning. The objective of this study was to explore how people with cancer comprehended Advance Care Plans and examine how accurately advance care planning documentation represented patient wishes. Methods: This study used a qualitative descriptive design. Data collection comprised interviews and an examination of participants’ existing advance care planning documentation. Participants included those who had any diagnosis of cancer with an advance care plan recorded: Refusal of Treatment Certificate; Statement of Choices; and/or Enduring Power of Attorney (Medical Treatment) at one cancer treatment centre. Results: Fourteen participants were involved in the study. Twelve participants were female (86%). The mean age was 77 (range: 61-91) and participants had completed their advance care planning documentation between 8 and 72 weeks prior to the interview (mean 33 weeks). Three themes were evident from the data: Incomplete advance care planning understanding and confidence; Limited congruence for attitude and documentation; Advance care planning can enable peace of mind. Complete advance care planning understanding was unusual; most participants demonstrated partial comprehension of their own advance care plan, and some indicated very limited understanding. Participants’ attitudes and their written document congruence was limited, but advance care planning was seen as helpful. Conclusions: This study highlighted advance care planning was not a completely accurate representation of patient wishes. There is opportunity to improve how patients comprehend their own advance care planning documentation

Are lay people good at recognising the symptoms of schizophrenia?

©2013 Erritty, Wydell. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Aim: The aim of this study was to explore the general public’s perception of schizophrenia symptoms and the need to seekhelp for symptoms. The recognition (or ‘labelling’) of schizophrenia symptoms, help-seeking behaviours and public awareness of schizophrenia have been suggested as potentially important factors relating to untreated psychosis. Method: Participants were asked to rate to what extent they believe vignettes describing classic symptoms (positive and negative) of schizophrenia indicate mental illness. They were also asked if the individuals depicted in the vignettes required help or treatment and asked to suggest what kind of help or treatment. Results: Only three positive symptoms (i.e., Hallucinatory behaviour, Unusual thought content and Suspiciousness) of schizophrenia were reasonably well perceived (above 70%) as indicating mental illness more than the other positive or negative symptoms. Even when the participants recognised that the symptoms indicated mental illness, not everyone recommended professional help. Conclusion: There may be a need to improve public awareness of schizophrenia and psychosis symptoms, particularly regarding an awareness of the importance of early intervention for psychosis

Dietary Compounds Influencing the Sensorial, Volatile and Phytochemical Properties of Bovine Milk

peer-reviewedThe main aim of this study was to evaluate the volatile profile, sensory perception, and phytochemical content of bovine milk produced from cows fed on three distinct feeding systems, namely grass (GRS), grass/clover (CLV), and total mixed ration (TMR). Previous studies have identified that feed type can influence the sensory perception of milk directly via the transfer of volatile aromatic compounds, or indirectly by the transfer of non-volatile substrates that act as precursors for volatile compounds. In the present study, significant differences were observed in the phytochemical profile of the different feed and milk samples. The isoflavone formonoetin was significantly higher in CLV feed samples, but higher in raw GRS milk, while other smaller isoflavones, such as daidzein, genistein, and apigenin were highly correlated to raw CLV milk. This suggests that changes in isoflavone content and concentration in milk relate to diet, but also to metabolism in the rumen. This study also found unique potential volatile biomarkers in milk (dimethyl sulfone) related to feeding systems, or significant differences in the concentration of others (toluene, p-cresol, ethyl and methyl esters) based on feeding systems. TMR milk scored significantly higher for hay-like flavor and white color, while GRS and CLV milk scored significantly higher for a creamy color. Milk samples were easily distinguishable by their volatile profile based on feeding system, storage time, and pasteurization

Falkland Island peatland development processes and the pervasive presence of fire

Acknowledgments RJP secured funding for this research from the Quaternary Research Association, University of York and the Russian Science Foundation (19-14-00102). We thank Paul Brickle and other members of the South Atlantic Environmental Research Institute for their help with logistics, David Large for valuable discussions about Falkland Islands peat and all landowners for access permission. This work is dedicated to Richard J. Payne who was tragically killed while climbing Peak 6477, a previously unclimbed subsidiary peak of Nanda Devi (Garhwal Himalayas) in May 2019. CRediT authorship contribution statement Dmitri Mauquoy: Conceptualization, Investigation, Writing - original draft, Writing - review & editing. Richard J. Payne: Conceptualization, Investigation. Kirill V. Babeshko: Investigation, Writing - original draft, Writing - review & editing. Rebecca Bartlett: Investigation, Writing - original draft, Writing - review & editing. Ian Boomer: Investigation. Hannah Bowey: Investigation. Chris D. Evans: Conceptualization, Writing - original draft, Writing - review & editing. Fin Ring-Hrubesh: Investigation. David Muirhead: Methodology, Investigation, Writing - original draft, Writing - review & editing. Matthew O’Callaghan: Investigation. Natalia Piotrowska: Investigation. Graham Rush: Investigation. Thomas Sloan: Investigation. Craig Smeaton: Methodology, Investigation, Writing - original draft. Andrey N. Tsyganov: Investigation, Writing - original draft, Writing - review & editing. Yuri A. Mazei: Investigation, Writing - original draft, Writing - review & editing.Peer reviewedPostprin

Long-term monitoring in primary care for chronic kidney disease and chronic heart failure: a multi-method research programme

Background: Long-term monitoring is important in chronic condition management. Despite considerable costs of monitoring, there is no or poor evidence on how, what and when to monitor. The aim of this study was to improve understanding, methods, evidence base and practice of clinical monitoring in primary care, focusing on two areas: chronic kidney disease and chronic heart failure. Objectives: The research questions were as follows: does the choice of test affect better care while being affordable to the NHS? Can the number of tests used to manage individuals with early-stage kidney disease, and hence the costs, be reduced? Is it possible to monitor heart failure using a simple blood test? Can this be done using a rapid test in a general practitioner consultation? Would changes in the management of these conditions be acceptable to patients and carers? Design: Various study designs were employed, including cohort, feasibility study, Clinical Practice Research Datalink analysis, seven systematic reviews, two qualitative studies, one cost-effectiveness analysis and one cost recommendation. Setting: This study was set in UK primary care. Data sources: Data were collected from study participants and sourced from UK general practice and hospital electronic health records, and worldwide literature. Participant: The participants were NHS patients (Clinical Practice Research Datalink: 4.5 million patients), chronic kidney disease and chronic heart failure patients managed in primary care (including 750 participants in the cohort study) and primary care health professionals. Interventions: The interventions were monitoring with blood and urine tests (for chronic kidney disease) and monitoring with blood tests and weight measurement (for chronic heart failure). Main outcome measures: The main outcomes were the frequency, accuracy, utility, acceptability, costs and cost-effectiveness of monitoring. Results: Chronic kidney disease: serum creatinine testing has increased steadily since 1997, with most results being normal (83% in 2013). Increases in tests of creatinine and proteinuria correspond to their introduction as indicators in the Quality and Outcomes Framework. The Chronic Kidney Disease Epidemiology Collaboration equation had 2.7% greater accuracy (95% confidence interval 1.6% to 3.8%) than the Modification of Diet in Renal Disease equation for estimating glomerular filtration rate. Estimated annual transition rates to the next chronic kidney disease stage are ≈ 2% for people with normal urine albumin, 3–5% for people with microalbuminuria (3–30 mg/mmol) and 3–12% for people with macroalbuminuria (> 30 mg/mmol). Variability in estimated glomerular filtration rate-creatinine leads to misclassification of chronic kidney disease stage in 12–15% of tests in primary care. Glycaemic-control and lipid-modifying drugs are associated with a 6% (95% confidence interval 2% to 10%) and 4% (95% confidence interval 0% to 8%) improvement in renal function, respectively. Neither estimated glomerular filtration rate-creatinine nor estimated glomerular filtration rate-Cystatin C have utility in predicting rate of kidney function change. Patients viewed phrases such as ‘kidney damage’ or ‘kidney failure’ as frightening, and the term ‘chronic’ was misinterpreted as serious. Diagnosis of asymptomatic conditions (chronic kidney disease) was difficult to understand, and primary care professionals often did not use ‘chronic kidney disease’ when managing patients at early stages. General practitioners relied on Clinical Commissioning Group or Quality and Outcomes Framework alerts rather than National Institute for Health and Care Excellence guidance for information. Cost-effectiveness modelling did not demonstrate a tangible benefit of monitoring kidney function to guide preventative treatments, except for individuals with an estimated glomerular filtration rate of 60–90 ml/minute/1.73 m2, aged < 70 years and without cardiovascular disease, where monitoring every 3–4 years to guide cardiovascular prevention may be cost-effective. Chronic heart failure: natriuretic peptide-guided treatment could reduce all-cause mortality by 13% and heart failure admission by 20%. Implementing natriuretic peptide-guided treatment is likely to require predefined protocols, stringent natriuretic peptide targets, relative targets and being located in a specialist heart failure setting. Remote monitoring can reduce all-cause mortality and heart failure hospitalisation, and could improve quality of life. Diagnostic accuracy of point-of-care N-terminal prohormone of B-type natriuretic peptide (sensitivity, 0.99; specificity, 0.60) was better than point-of-care B-type natriuretic peptide (sensitivity, 0.95; specificity, 0.57). Within-person variation estimates for B-type natriuretic peptide and weight were as follows: coefficient of variation, 46% and coefficient of variation, 1.2%, respectively. Point-of-care N-terminal prohormone of B-type natriuretic peptide within-person variability over 12 months was 881 pg/ml (95% confidence interval 380 to 1382 pg/ml), whereas between-person variability was 1972 pg/ml (95% confidence interval 1525 to 2791 pg/ml). For individuals, monitoring provided reassurance; future changes, such as increased testing, would be acceptable. Point-of-care testing in general practice surgeries was perceived positively, reducing waiting time and anxiety. Community heart failure nurses had greater knowledge of National Institute for Health and Care Excellence guidance than general practitioners and practice nurses. Health-care professionals believed that the cost of natriuretic peptide tests in routine monitoring would outweigh potential benefits. The review of cost-effectiveness studies suggests that natriuretic peptide-guided treatment is cost-effective in specialist settings, but with no evidence for its value in primary care settings. Limitations: No randomised controlled trial evidence was generated. The pathways to the benefit of monitoring chronic kidney disease were unclear. Conclusions: It is difficult to ascribe quantifiable benefits to monitoring chronic kidney disease, because monitoring is unlikely to change treatment, especially in chronic kidney disease stages G3 and G4. New approaches to monitoring chronic heart failure, such as point-of-care natriuretic peptide tests in general practice, show promise if high within-test variability can be overcome

Left dorsolateral prefrontal cortex supports context-dependent prioritisation of off-task thought

When environments lack compelling goals, humans often let their minds wander to thoughts with greater personal relevance; however, we currently do not understand how this context-dependent prioritisation process operates. Dorsolateral prefrontal cortex (DLPFC) maintains goal representations in a context-dependent manner. Here, we show this region is involved in prioritising off-task thought in an analogous way. In a whole brain analysis we established that neural activity in DLPFC is high both when ‘on-task’ under demanding conditions and ‘off-task’ in a non-demanding task. Furthermore, individuals who increase off-task thought when external demands decrease, show lower correlation between neural signals linked to external tasks and lateral regions of the DMN within DLPFC, as well as less cortical grey matter in regions sensitive to these external task relevant signals. We conclude humans prioritise daydreaming when environmental demands decrease by aligning cognition with their personal goals using DLPFC

Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells

Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca2+) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca2+ signaling in hPAECs by inhibiting the sarco-endoplasmic Ca2+-ATPase (SERCA) which is involved in the regulation of the intracellular Ca2+ homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes

Proteomic Profiling of Mesenchymal Stem Cell Responses to Mechanical Strain and TGF-β1

Mesenchymal stem cells (MSCs) are a potential source of smooth muscle cells (SMCs) for constructing tissue-engineered vascular grafts. However, the details of how specific combinations of vascular microenvironmental factors regulate MSCs are not well understood. Previous studies have suggested that both mechanical stimulation with uniaxial cyclic strain and chemical stimulation with transforming growth factor-β1 (TGF-β1) can induce smooth muscle markers in MSCs. In this study, we investigated the combined effects of uniaxial cyclic strain and TGF-β1 stimulation on MSCs. By using a proteomic analysis, we found differential regulation of several proteins and genes, such as the up-regulation of TGF-β1-induced protein ig-h3 (BGH3) protein levels by TGF-β1 and up-regulation of calponin 3 protein level by cyclic strain. At the gene expression level, BGH3 was induced by TGF-β1, but calponin 3 was not significantly regulated by mechanical strain or TGF-β1, which was in contrast to the synergistic up-regulation of calponin 1 gene expression by cyclic strain and TGF-β1. Further experiments with cycloheximide treatment suggested that the up-regulation of calponin 3 by cyclic strain was at post-transcriptional level. The results in this study suggest that both mechanical stimulation and TGF-β1 signaling play unique and important roles in the regulation of MSCs at both transcriptional and post-transcriptional levels, and that a precise combination of microenvironmental cues may promote MSC differentiation

Change in maternal body mass index is associated with offspring body mass index: a 21-year prospective study

High body-mass index (BMI; defined as 25 kg/m(2) or greater) is associated with increased risk of cancer. To inform public health policy and future research, we estimated the global burden of cancer attributable to high BMI in 2012